Angiogenesis is a regulated process involving the formation of new blood vessels. It plays an essential role in normal growth, embryonic development, wound healing, and other physiological processes (Yancopoulos et al. (2000) Nature 407(6801):242-8). Moreover, de novo angiogenesis is involved in several disease states including cancer, where the formation of new “embryonic-like” blood vessels (referred to as neovascularization herein) appear that differ from normal vasculature with regards to structure and function (Hanahan and Weinberg (2000) Cell 100(1):57-70). A number of in vivo and in vitro studies have demonstrated biological differences between normal and disease-associated vasculature as determined using various model systems of angiogenesis offering the ability to develop novel anti-angiogenic compounds that can selectively inhibit vessel formation of the embryonic-type, tumor-associated endothelial-type for therapy of neovascular disease.
In light of these opportunities for therapy, an intense search for potential targets that can specifically inhibit tumor and other neovascular disease-associated endothelial cell growth and function is ongoing. In an attempt to identify such targets, strategies have been designed to identify cell surface antigens of tumor stroma as well as isolate specific proteins or RNA that are expressed in neovascular endothelial cells (Rettig et al. (1992) PNAS 89(22):10832-6; St. Croix et al. (2000) Science 289: 1197-1202). These strategies have identified a cell surface protein called tumor endothelial marker 1 (TEM-1), also known as endosialin or CD248. TEM-1 is expressed on tumor-associated pericytes, tumor stromal cells and directly on a subset of malignant cells. Pericytes are specialized cells that support the formation of blood vessels that support blood to tumors for their growth and survival. Expression of TEM-1 in tumors has been observed by several independent laboratories and experiments, and blocking endosialin function has been shown to inhibit tumor growth and metastasis.
In cancer it is believed that neovascularization is important to supply tumors with blood, providing nutrients to support largely uncontrolled growth. Thus, proteins, such as TEM-1, that are differentially associated with tumor vasculature have become potential therapeutic targets for the treatment of cancer. The development of antibodies that can specifically target TEM-1 offers the ability to treat these diseases. It is also understood that earlier detection of cancer improves survival rates and quality of life. To improve the likelihood of early detection and effective treatment, a need exists for non-invasive methods for detecting cancers, monitoring existing cancers, and assessing therapeutic efficacy.